The objectives of this project concern the systematic manipulation of the hormonal and humoral milieu in the developing rat, followed by quantitative morphological analysis of cell proliferation, neuronal differentiation and cell migration in the brain. These studies are based on the hypothesis that hormones and neurohumoral agents (neutrotransmitters) may modulate th rate of neurogenesis during pre-and postnatal development. The first part of this investigation consists of a comparison of the effects of neonatal administration of glucocorticoids and thyroxine on postnatal cell formation in the cerebellar cortex and hippocampus. Since both treatments lead to cell deficits in the developing brain, the main purpose of this study is to determine how this deficit occurs and what cell types are affected using 3H-thymidine autoradiography, quantitative light microscopic methods and electron microscopy. The second part of this program is designed to test the hypothesis that early forming neurons may influence the time of onset of differentiation of their target cells, leading to a sequential turning off of cell proliferation in the embryonic neuroepithelium. The monoamine neurons wwll be used as a model since they are known to begin their differentiation and transmitter synthesis very early in gestation, several days prior to the time of differentiation of their target cells. Since pilot studies have already indicated that treatment of the pregnant mother with monoamine depleting drugs can change the time course of differentiation of such monoamine receptive cells, these studies will be repeated and compared to the effects of administration of monoamine precursors. Since pilot studies have also indicated that maternal stress may influence embryonic neuronal differentiation (and glucocorticoids may be elevated in the stressed pregnant female), the effects of glucocorticoid administration to the pregnant mother will also be examined. Such data will help not only to evaluate the possibility that early forming monoamine neurons may influence the time of differentiation of their target cells, but may also provide a model system within which to test the effects of drugs, hormones and maternal influences on prenatal neurogenesis.